Administration of misoprostol by trained traditional birth attendants to prevent postpartum haemorrhage in homebirths in Pakistan: a randomised placebo-controlled trial.

OBJECTIVE: to determine if misoprostol is safe and efficacious in preventing postpartum haemorrhage (PPH) when administered by trained traditional birth attendants (TBA) at home deliveries. DESIGN: a randomised, double-blind, placebo-controlled trial. SETTING: Chitral, Khyber Pakhtunkhwa Province, Pakistan. POPULATION: a total of 1119 women giving birth at home. METHODS: from June 2006 to June 2008, consenting women were randomised to receive 600 microg oral misoprostol (n = 534) or placebo (n = 585) after delivery to determine whether misoprostol reduced the incidence of PPH (≥ 500 ml). MAIN OUTCOME MEASURES: the primary outcomes were measured blood loss ≥ 500 ml after delivery and drop in haemoglobin >2 g/dl from before to after delivery. RESULTS: oral misoprostol was associated with a significant reduction in the rate of PPH (≥ 500 ml) (16.5 versus 21.9%; relative risk 0.76, 95% CI 0.59-0.97). There were no measurable differences between study groups for drop in haemoglobin >2 g/dl (relative risk 0.79, 95% CI 0.62-1.02); but significantly fewer women receiving misoprostol had a drop in haemoglobin >3 g/dl, compared with placebo (5.1 versus 9.6%; relative risk 0.53, 95% CI 0.34-0.83). Shivering and chills were significantly more common with misoprostol. There were no maternal deaths among participants. CONCLUSIONS: postpartum administration of 600 microg oral misoprostol by trained TBAs at home deliveries reduces the rate of PPH by 24%. Given its ease of use and low cost, misoprostol could reduce the burden of PPH in community settings where universal oxytocin prophylaxis is not feasible. Continual training and skill-building for TBAs, along with monitoring and evaluation of programme effectiveness, should accompany any widespread introduction of this drug.

Treatment of postpartum hemorrhage with misoprostol.

A literature review was conducted to determine whether misoprostol is an effective treatment for postpartum hemorrhage (PPH) and in what dose. All English language articles published before March 2007 reporting on misoprostol for treatment of PPH were reviewed. Unpublished data previously presented at international scientific meetings were also included in the review. Little evidence exists in support of misoprostol for treatment of postpartum hemorrhage (PPH). Nonetheless, PPH remains a major killer of women worldwide, and new treatment options are widely sought. For this reason, we recommend a single dose of misoprostol 600 microg oral or sublingual for PPH treatment in instances when other treatments have either failed to work or are not available.

Prevention of postpartum hemorrhage with misoprostol.

As a stable, orally active and cheap uterotonic, misoprostol would appear ideally suited to the prevention of postpartum hemorrhage (PPH) in the developing world. Following numerous clinical trials, it appears that misoprostol prophylaxis using an oral or sublingual dose of 600 microg is more effective than placebo at preventing PPH in community births (relative risk 0.59, 95% confidence intervals 0.41-0.84), but not in hospital settings (RR 1.23, 95% CI 0.86-1.74). It is, however, not as effective as injectable oxytocin (RR 1.34, 95% CI 1.16 to 1.55). Misoprostol is therefore indicated for prevention of PPH in settings where injectable conventional uterotonics are not available. In the event of continued hemorrhage, a minimum of 2 h should lapse after the original dose before a second dose is given. If the initial dose was associated with pyrexia or marked shivering, at least 6 h should lapse before the second dose is given.

A randomized, placebo-controlled trial of intermittent preventive treatment with sulphadoxine-pyrimethamine in Gambian multigravidae.

We investigated the ability of intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine/pyrimethamine to prevent anaemia and low birthweight in Gambian multigravidae. Between July 2002 and February 2004, 2688 multigravidae living in a rural area of The Gambia received SP (1346 women) or placebo (1342 women) up to four times during pregnancy and were followed until 6-weeks post-partum. Shortly after delivery, 10.7% of women in the intervention group and 8.8% in the control group were severely anaemic [Hb < 7 g/dl, risk difference = 0.02 (95% CI -0.01, 0.04), P = 0.17]. The overall mean birthweight of infants born to women who had received SP (3103 g) was very similar to that observed in infants born to women in the control group [3075 g; difference = 28 g (95% CI -11 g, 67 g), P = 0.16]. However, among women who did not use a bednet (either insecticide treated or untreated), infants born to women who had received SP weighed more than infants born to women in the control group [3147 g vs. 3044 g; difference 143 g (95% CI 53 g, 232 g), interaction test P < 0.001]. This study did not show that IPTp with SP benefited Gambian multigravidae overall but that it may benefit a sub-group of women who do not use a bednet. In areas such as The Gambia, provision of insecticide-treated bednets to multigravidae may provide an adequate means of protection against malaria in pregnancy without the need for additional IPTp.

Cervical human papillomavirus infection and squamous intraepithelial lesions in rural Gambia, West Africa: viral sequence analysis and epidemiology.

The development of effective strategies against cervical cancer in Africa requires accurate type specific data on human papillomavirus (HPV) prevalence, including determination of DNA sequences in order to maximise local vaccine efficacy. We have investigated cervical HPV infection and squamous intraepithelial lesions (SIL) in an unselected cohort of 1061 women in a rural Gambian community. Squamous intraepithelial lesions was diagnosed using cytology and histology, HPV was typed by PCR-ELISA of DNA extracts, which were also DNA sequenced. The prevalence of cervical HPV infection was 13% and SIL were observed in 7% of subjects. Human papillomavirus-16 was most prevalent and most strongly associated with SIL. Also common were HPV-18, -33, -58 and, notably, -35. Human papillomavirus DNA sequencing revealed HPV-16 samples to be exclusively African type 1 (Af1). Subjects of the Wolof ethnic group had a lower prevalence of HPV infection while subjects aged 25-44 years had a higher prevalence of cervical precancer than older or younger subjects. This first report of HPV prevalence in an unselected, unscreened rural population confirms high rates of SIL and HPV infection in West Africa. This study has implications for the vaccination of Gambian and other African populations in the prevention of cervical cancer.

Comparison of non-invasive sampling methods for detection of HPV in rural African women.

BACKGROUND: The prevalence of cervical cancer is extremely high in low income countries, primarily because of a lack of cytological screening. The link between human papillomavirus (HPV) and cervical cancer has long been recognised, and it has been suggested that isolated HPV testing in women who do not participate in existing screening programmes may be used to identify women at higher risk of developing cervical cancer. This community based study compares two self administered techniques for detecting HPV (tampons and self administered swabs) with a clinician directed technique, the cervical cytobrush. METHODS: 377 rural women were interviewed and of these 210 women had full gynaecological examination, and accepted all three sampling methods for HPV. HPV typing of DNA extracts was performed using polymerase chain reaction and enzyme linked immunosorbent assay techniques. RESULTS: Using the cervical cytobrush as the gold standard, self administered swabs (SAS) showed a sensitivity of 63.9%, and tampons showed a sensitivity of 72.4%. The acceptability of these two tests was 97.1% and 84.6% respectively. When combining acceptability with sensitivity, the SAS detected 61.9% and the tampons detected 60.9% of the true positives. CONCLUSION: In a setting where women are at a considerable risk of developing cervical cancer, with no access to a formal screening programme, self directed HPV testing could be a useful screening tool in identifying those women at increased risk who may require further investigation.

Bacterial vaginosis in relation to menstrual cycle, menstrual protection method, and sexual intercourse in rural Gambian women.

OBJECTIVE: To examine the occurrence of bacterial vaginosis (BV) over the menstrual cycle and in relation to menstrual protection materials and sexual intercourse in a rural African setting. METHODS: Married, regularly menstruating female volunteers were asked to collect self administered swabs on alternate days through four menstrual cycles. BV was assessed using Nugent scores. Menstruation and reported sexual intercourse data were recorded contemporaneously. A crossover design comparing traditional and modern menstrual protection methods was incorporated. Multivariate logistic regression was used to examine associations with BV. RESULTS: 30 women completed four menstrual cycles in the study. Completeness and validity of data from the self administered swabs was high. Greater frequencies of BV were found for all women in the second week of the menstrual cycle relative to days 14+, and markedly higher frequencies of BV were found in the first week in women with infrequent BV. BV was (non-significantly) more frequent when modern pads were used compared with traditional cloths. No association was found between BV and intercourse reported in the previous 4 days; or between the frequency of reported intercourse in one menstrual cycle and BV in either the same menstrual cycle or the next. CONCLUSIONS: Similar transient fluctuations over the menstrual cycle were found to those in industrialised countries. We found no evidence that sexual intercourse was associated with increased frequency of BV. Our data do not support hypotheses that menstrual hygiene materials might explain the high prevalences of BV found in sub-Saharan Africa compared to industrialised countries.

Syncytiotrophoblast degradation and the pathophysiology of the malaria-infected placenta.

Malaria is associated with excessive parasitic infection of the placenta and a reduction in neonatal birthweight. This study has investigated placental cell death in women with active and past malarial infection. Term placentae, with and without malarial pathology, were obtained from women in The Gambia. Active and past malaria infections were identified in placental sections and histological examination was used to determine the number of villi, the incidence of apoptosis, syncytial degradation, fibrinoid deposition and the frequency of syncytial knots. Placentae with active malaria infection showed erythrocyte adhesion of infected cells to syncytiotrophoblast, syncytial degradation, increased syncytial knotting and, in rare cases, localized destruction of the villi. Past malarial infection was characterized by syncytiotrophoblast disruption and fibrin-type fibrinoid (FTF) deposition. Perivillous FTF deposition was consistent with increased syncytial lesions and both increased lesions and syncytial knots were associated with birthweight reductions. Active malaria infection produced no alteration in placental apoptosis. The numbers of chorionic villi remained unchanged and infiltration of inflammatory cells, although not measured directly, appeared to be non-pervasive within the infected tissue. These observations establish a direct link between malaria parasitic infection and syncytiotrophoblast damage. The placental rejection of parasite-affected syncytia may invoke structural changes to compensate for inadequate placental exchange. Syncytial destruction could have serious implications; impairing fetal growth and in some rare cases, providing a previously unrecognized pathway to congenital infection.

Maternal mortality and access to obstetric services in West Africa.

OBJECTIVES: Process evaluation has become the mainstay of safe motherhood evaluation in developing countries, yet the extent to which indicators measuring access to obstetric services at the population level reflect levels of maternal mortality is uncertain. In this study we examine the association between population indicators of access to obstetric care and levels of maternal mortality in urban and rural West Africa. METHODS: In this ecological study we used data on maternal mortality and access to obstetric services from two population-based studies conducted in 16 sites in eight West African countries: the Maternal Mortality and Obstetric Care in West Africa (MAMOCWA) study in rural Sénégal, Guinea-Bissau and The Gambia and the Morbidité Maternelle en Afrique de l'Ouest (MOMA) study in urban Burkina Faso, Côte d'Ivoire, Mali, Mauritanie, Niger and Sénégal. RESULTS: In rural areas, maternal mortality, excluding early pregnancy deaths, was 601 per 100,000 live births, compared with 241 per 100,000 for urban areas [RR = 2.49 (CI 1.77-3.59)]. In urban areas, the vast majority of births took place in a health facility (83%) or with a skilled provider (69%), while 80% of the rural women gave birth at home without any skilled care. There was a relatively close link between levels of maternal mortality and the percentage of births with a skilled attendant (r = -0.65), in hospital (r = -0.54) or with a Caesarean section (r = -0.59), with marked clustering in urban and rural areas. Within urban or rural areas, none of the process indicators were associated with maternal mortality. CONCLUSION: Despite the limitations of this ecological study, there can be little doubt that the huge rural-urban differences in maternal mortality are due, at least in part, to differential access to high quality maternity care. Whether any of the indicators examined here will by themselves be good enough as a proxy for maternal mortality is doubtful however, as more than half of the variation in mortality remained unexplained by any one of them.

Changes in house design reduce exposure to malaria mosquitoes.

House design may affect an individual's exposure to malaria parasites, and hence to disease. We conducted a randomized-controlled study using experimental huts in rural Gambia, to determine whether installing a ceiling or closing the eaves could protect people from malaria mosquitoes. Five treatments were tested against a control hut: plywood ceiling; synthetic-netting ceiling; insecticide-treated synthetic-netting ceiling (deltamethrin 12.5 mg/m2); plastic insect-screen ceiling; or the eaves closed with mud. The acceptability of such interventions was investigated by discussions with local communities. House entry by Anopheles gambiae, the principal African malaria vector, was reduced by the presence of a ceiling: plywood (59% reduction), synthetic-netting (79%), insecticide-treated synthetic-netting (78%), plastic insect-screen (80%, P < 0.001 in all cases) and closed eaves (37%, ns). Similar reductions were also seen with Mansonia spp., vectors of lymphatic filariasis and numerous arboviruses. Netting and insect-screen ceilings probably work as decoy traps attracting mosquitoes into the roof space, but not the room. Ceilings are likely to be well accepted and may be of greatest benefit in areas of low to moderate transmission and when used in combination with other malaria control strategies.

Absence of association between delayed type hypersensitivity to tuberculin and atopy in children in The Gambia.

BACKGROUND: An inverse association between delayed type hypersensitivity to tuberculin and atopy has been observed in children, suggesting that exposure to mycobacteria may influence the immune response to allergens. OBJECTIVE: To investigate the relationship between tuberculin responses and atopy in children living in three different environments in The Gambia. METHODS: In this cross-sectional study a total of 507 school-aged children were recruited from rural, urban poor or urban affluent communities. They were assessed for skin responses to five common allergens and tuberculin, presence of bacille Calmette-Guérin (BCG) scar, presence of intestinal parasites, and total serum IgE. Atopy was defined as the presence of a skin prick test response > or = 3 x 3 mm to at least one allergen. RESULTS: The overall prevalence of atopy was 33% but there was a significant variation among the three study groups. The prevalence of atopy was 22% in urban poor, 36% in urban affluent, and 43% in rural children. Controlling for potential confounding factors, children in the rural community had a significantly higher odds ratio, 3.3 (95% confidence interval 1.8-6.0) of being atopic than children from the urban poor community. No association between atopy and tuberculin response or BCG scar was observed in any of the three groups. Serum IgE levels were higher among children of the urban poor group but were not associated with tuberculin response or BCG scar in any of the groups. CONCLUSION: Environmental factors have an important influence on the development of atopy in children in The Gambia but delayed type hypersensitivity to tuberculin is not a protective factor.

Performance of the rapid plasma reagin and the rapid syphilis screening tests in the diagnosis of syphilis in field conditions in rural Africa.

OBJECTIVES: To assess the rapid plasma reagin (RPR) test performance in the field and to evaluate a new rapid syphilis test (RST) as a primary screen for syphilis. METHODS: 1325 women of reproductive age from rural communities in the Gambia were tested for syphilis seropositivity using a RPR 18 mm circle card and a RST strip. Within 1 week a repeat RPR and a TPHA test were carried out using standard techniques in the laboratory. RESULTS: Comparing field tests to a diagnosis of "active" syphilis defined as laboratory RPR and TPHA positive, the RPR test was 77.5% sensitive and 94.1% specific; the RST was 75.0% sensitive and 95.2% specific. The RST was easier to use and interpret than the RPR test especially where field conditions were difficult. In this setting with a low prevalence of syphilis in the community (3%), the chance of someone with a positive test being confirmed as having serologically active syphilis was less than 50% for both tests. CONCLUSIONS: The appropriateness of syphilis screening using RPR testing in antenatal clinics and health centres should be questioned if there is a low prevalence in the population, conditions for testing are poor, and resources limited. There is still an urgent need for an appropriate rapid syphilis test for field use.

Short-range attractiveness of pregnant women to Anopheles gambiae mosquitoes.

Malaria is a major cause of illness and an indirect cause of mortality in pregnant women. It can also cause stillbirths and low-birthweight babies. We have shown previously that pregnant women attracted twice as many Anopheles gambiae mosquitoes, the principal African malaria vector, as their non-pregnant counterparts over distances of about 15 m. In the current study (in 1998/99) we compared the short-range attractiveness of both pregnant and non-pregnant women sleeping under untreated bednets in Gambian villages. First, we measured the rate of mosquito entry under bednets and, second, we calculated the proportion of mosquitoes biting mothers under each bednet compared to their children. The feeding preference of An. gambiae collected under nets was determined by DNA fingerprinting blood samples from human subjects sleeping under each bednet and comparing these to fingerprints obtained from mosquito bloodmeals. Pregnant women were more attractive to An. gambiae mosquitoes than non-pregnant women under an untreated bednet. The number of mosquitoes entering bednets each night was 1.7-4.5 times higher in the pregnant group (P = 0.02) and pregnant women also received a higher proportion of bites under the bednets than did non-pregnant women (70% vs 52%, P = 0.001). This study clearly demonstrates that pregnant women are more exposed to malaria parasites than other women, which contributes to the greater vulnerability of pregnant women to malaria.

Increased risk for malaria in chronically malnourished children under 5 years of age in rural Gambia.

Malaria and malnutrition cause high morbidity and mortality in rural sub-Saharan Africa. To explore the relationship between nutritional status and malaria, a cohort of Gambian children under 5 years of age was followed weekly during one malaria season. Anthropometric measurements were made at the beginning and at the end of the season. A total of 55/107 (51.4 per cent) children with baseline stunting, defined as having a height-for-age z-score below -2 standard deviations, subsequently experienced malaria episodes, compared to 145/380 (38.2 per cent) children who were not stunted (RR = 1.35; 95 per cent CI, 1.08-1.69; p value = 0.01). Neither wasting (weight-for-height z-score below -2 standard deviations) nor undernutrition (weight-for-age z-score below -2 standard deviations) influenced susceptibility to malaria. Adjustment for characteristics of age, sex, and ethnicity did not significantly change the risk ratios. Malaria had no effect on the nutritional status from the beginning to the end of the malaria season. Our findings suggest that chronically malnourished children may be at higher risk for developing malaria episodes.

A template for improved prevention and control of cardiovascular disease in sub-Saharan Africa.

Cardiovascular disease (CVD) is rapidly becoming an important public health problem in sub-Saharan Africa, yet the response so far is often minimal and inadequate. While there is, undoubtedly, a 'double burden of disease' (persisting infectious diseases co-existing with emerging non-communicable disease), this is hardly reflected in current health planning, possibly due to a limited appreciation of the changing pattern of CVD and CVD risk factor exposure. In a situation where there are also considerable budget constraints and well-established infectious disease priorities, it is difficult to implement effective interventions for prevention or treatment of CVD. Yet such planning is urgently needed and a template for a comprehensive programme, adaptable to local situations, is presented here. The first step is to raise awareness and create evidence-based commitment among policy-makers, which could lead to the establishment of a multi-sectoral CVD unit at national level. Programmes need to focus on prevention of modifiable risk factors at population level, involving a wide range of institutions and individuals. Recommended strategies include decentralizing the design and implementation of programmes, with appropriate standardized surveillance of major risk factors, all complemented by operational, epidemiological and basic research.

Atopy, intestinal helminth infection and total serum IgE in rural and urban adult Gambian communities.

BACKGROUND: The rarity of atopy in traditional societies has been attributed to high parasite-driven blocking IgE concentrations. Information is lacking on the relationship between atopy, IgE and intestinal helminth infection in African populations. OBJECTIVE: To determine the prevalence of atopy and intestinal helminth infection and to relate these to wheeze history and serum total IgE in a community sample of adults from an urban (Banjul) and a rural (Farafenni) area of the Gambia. METHODS: Six hundred and ninety-three adults were interviewed about respiratory symptoms using a modified version of the IUTLD questionnaire, and had skin prick testing using four allergens. Stools were examined after formol-ether concentration. Total serum IgE concentration was measured in a subset of participants. RESULTS: The prevalence of atopy (mean weal diameter > or = 3 mm) in the urban and rural area was 35.3% and 22.5% (P = 0.05); D. pteronyssinus and Mold mix being the common sensitizing allergens. Prevalence of wheeze in the previous 12 months was 4.4% and 3.5% for the urban and rural areas, respectively. Wheezing was not significantly associated with atopy. Seventeen per cent of urban and 8.2% of rural subjects had helminths detected in stools. There was an inverse association between atopy and intestinal helminth infection; 7% of atopic subjects had helminths, compared to 13% of non-atopic subjects (unadjusted odds ratio 0.51, 95%CI 0.24-1.1, P = 0.09; adjusted odds ratio 0.37, 95%CI 0.15-0.92, P = 0.03). Non-atopics had total serum IgE concentrations about 2.5 times the upper limit of the reference range in non-atopic Western populations. Geometric mean total serum IgE concentration was significantly higher among atopic subjects (570 IU/mL, IQR 91-833) than non-atopic subjects (259 IU/mL, IQR 274-1303) (P < 0.001). IgE concentration was not associated with the presence of helminth infection. CONCLUSION: Further studies are needed to clarify why asthma is still relatively uncommon in spite of the prevalence of atopy in Gambian adults. Our data are also compatible with the idea that atopy might protect against helminth infection.

Asthma, smoking and chronic cough in rural and urban adult communities in The Gambia.

BACKGROUND: Asthma is reported to be rare in traditional rural communities, but is thought to be increasing as lifestyles become more urbanized or 'western'. OBJECTIVES: A community-based survey of non-communicable diseases was conducted from October 1996 to June 1997, and included comparison of the prevalence of asthma, smoking and chronic cough in rural and urban Gambia. METHODS: A cluster sample survey was conducted in a random sample of rural and urban adults (> or = 15 years of age). Subjects were asked about respiratory symptoms using a locally adapted version based on the IULTD questionnaire. Spirometry (basal, methacholine provocation and reversibility with a bronchodilator) and skin prick tests were performed on a randomly selected subsample of all subjects and those who, when interviewed, said they wheezed or had been diagnosed as asthmatic by a doctor. RESULTS: Out of 2166 participants in the urban population, 4.1% reported having had wheezing or whistling in the chest in the previous 12 months, 3.6% reported doctor-diagnosed asthma, and 0.6% chronic cough. In the rural population with 3223 participants these figures were 3.3%, 0.7% and 1.2%, respectively. Wheeze was more common in women, cough for 3 months of the year was more common in the age-groups 45+. Those who reported that they currently smoked accounted for 34% in urban and 42% in rural men. Figures were much lower for women (1.5% and 6.0%). Seven out of 574 randomly selected subjects (1.4%) exhibited bronchial hyper-responsiveness to methacholine challenge. Four of 133 (3.0%) people with self-reported wheeze and 3/69 (4.3%) participants with doctor-diagnosed asthma reacted positively on bronchial provocation with methacholine. There was a remarkably high prevalence of positive skin prick tests to aeroallergens: 38% in participants with a history of wheeze and 27% in those without. CONCLUSION: The prevalence of wheeze (particularly in association with bronchial hyper-responsiveness) was low in both rural and urban Gambia. This is in contrast to the relatively high prevalence of positive skin prick tests to aeroallergens (in both wheezers and non-wheezers), questioning the mechanisms of interaction between allergy and asthma and the presence of protective factors against asthma in this West African population. The high smoking rates justify international concern about tobacco marketing in developing societies.

Do untreated bednets protect against malaria?

Bednets are thought to offer little, if any, protection against malaria, unless treated with insecticide. There is also concern that the use of untreated nets will cause people sleeping without nets to receive more mosquito bites, and thus increase the malaria risk for other community members. Regular retreatment of nets is therefore viewed as critical for malaria control. However, despite good uptake of nets, many control programmes in Africa have reported low re-treatment rates. We investigated whether untreated bednets had any protective benefit (in October and November 1996) in The Gambia where nets, although widely used, are mostly untreated. Cross-sectional prevalence surveys were carried out in 48 villages and the risk of malaria parasitaemia was compared in young children sleeping with or without nets. Use of an untreated bednet in good condition was associated with a significantly lower prevalence of Plasmodium falciparum infection (51% protection [95% CI 34-64%], P < 0.001). This finding was only partly explained by differences in wealth between households, and children in the poorest households benefited most from sleeping under an untreated net (62% protection [14-83%], P = 0.018). There was no evidence that mosquitoes were diverted to feed on children sleeping without nets. These findings suggest that an untreated net, provided it is in relatively good condition, can protect against malaria. Control programmes should target the poorest households as they may have the most to gain from using nets.

Risk factors for gametocyte carriage in Gambian children.

A widespread reduction in Plasmodium falciparum gametocyte prevalence could reduce malaria transmission. After infection with P. falciparum, a variable proportion of people are found to be gametocytemic. We analyzed risk factors associated with gametocytemia at presentation and 7 days later. We enrolled 1,198 children in 2 antimalarial drug trials between September and December 1998. The children were assigned to 1 of 4 treatment groups: chloroquine only; pyrimethamine-sulfadoxine (PSD) only; PSD combined with 1 dose of artesunate; and PSD combined with 3 doses of artesunate. By the time of enrollment, 200 (17%) of 1,198 children were gametocyte carriers. Three independent risk factors were associated with gametocytemia at enrollment. Children with anemia were more likely to carry gametocytes, whereas children with fever (> 37.4 degrees C) or high parasite densities (> 100,000 parasites/microL) were less frequently gametocyte carriers. Children with at least 2 of the risk factors were 4 times more likely to be gametocytemic than children with < 2 risk factors (odds ratio [OR], 4.4; 95% confidence interval [CI], 2.7-7.1). Seven days after the start of treatment, 355 (37%) of 466 assessable children were found to be gametocyte carriers. Children treated with PSD alone had a significantly higher risk of being gametocytemic by Day 7 compared with children in the other 3 treatment groups. In the subgroup of children who had no detectable gametocytes on enrollment, the effect of treatment with PSD + 3 doses of artesunate was most marked. Nineteen (10%) of 198 children treated with PSD + 3 doses of artesunate became gametocytemic, in contrast to 184 (57%) of 321 children treated with PSD alone (OR, 12.7; 95% CI, 7.3-22.1). Early treatment with highly effective antimalarial therapy has the greatest chance of preventing gametocytemia. The choice of a first-line antimalarial drug for uncomplicated malaria should not only take into consideration the ablation asexual parasitemia but also the suppression of gametocytemia.

The safety of the combination artesunate and pyrimethamine-sulfadoxine given during pregnancy.

Malaria during pregnancy is associated with an increased risk of severe anaemia and low-birthweight babies. Effective intermittent therapy with pyrimethamine-sulfadoxine (PSD) decreases parasitaemia and severe anaemia and improves birthweight in areas where Plasmodium falciparum is sensitive to this drug. Increasing resistance to PSD is a concern and alternative antimalarial regimens during pregnancy are needed. Artesunate with PSD is a promising antimalarial combination but few data are available on the safety of artemisinins when taken during pregnancy. Outcome of pregnancy was evaluated for 287 women in The Gambia who were exposed in June 1999 to a single dose of the combination artesunate and PSD during a mass drug administration and 172 women who were not exposed. Women who received placebo (40) and those who did not participate in the mass drug administration (132) comprised the non-exposed group. There was no difference in the proportion of abortions, stillbirths, or infant deaths among those exposed or not exposed to the drugs. The mean weight of 18 infants born to mothers who had received artesunate and PSD during the third trimester was 3.10 kg compared to a mean weight of 2.62 kg of the 10 infants of untreated mothers (adjusted P value = 0.05). We found no evidence of a teratogenic or otherwise harmful effect of gestational exposure to artesunate and PSD. Treatment of a self-selected group of pregnant women with PSD and artesunate during pregnancy was associated with a greater birthweight, which may have resulted from clearance of malaria parasites. However, the influence of confounding factors cannot be excluded.